A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs

Bauer, Christiane K.; Schäfer, Roland M.; Schiemann, D. A.; Reid, Gordon; Hanganu, Ileana L.; Schwarz, Jürgen R.

doi:10.1016/s0303-7207(98)00241-x

Cited by 66 publications

(72 citation statements)

References 34 publications

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“…The increase in prolactin secretion induced by the erg current block in lactotrophs has been measured with the reverse hemolytic plaque assay [47]. The plaque area is a semiquantitative measure of prolactin secretion from a single lactotroph.…”

Section: Function Of the Erg Current In The Regulation Of Prolactin Smentioning

confidence: 99%

Functions of erg K⁺ channels in excitable cells

Schwarz

Bauer

2004

J Cellular Molecular Medi

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Ether-à-go-go-related gene (erg) channels are voltage-dependent K + channels mediating inward-rectifying K + currents because of their peculiar gating kinetics. These characteristics are essential for repolarization of the cardiac action potential. Inherited and acquired malfunctioning of erg channels may lead to the long QT-syndrome. However, erg currents have also been recorded in many other excitable cells, like smooth muscle fibres of the gastrointestinal tract, neuroblastoma cells or neuroendocrine cells. In these cells erg currents contribute to the maintenance of the resting potential. Changes in the resting potential are related to cell-specific functions like increase in hormone secretion, frequency adaptation or increase in contractility.

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Section: Function Of the Erg Current In The Regulation Of Prolactin Smentioning

confidence: 99%

Functions of erg K⁺ channels in excitable cells

Schwarz

Bauer

2004

J Cellular Molecular Medi

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“…HERG and the three known rat ERG isoforms are expressed in the nervous system, and although ERG-2 was thought to be restricted to a small subpopulation of neurons (8), we found ERG-2 mRNA in rat microglia (1). ERG channels in neurons can modulate the resting potential (9), spike frequency (10), hormonal secretion (11,12), and neuritogenesis (9, 13), although some roles have only been studied in cell lines. We previously identified ERG currents and ERG-1 protein in the brain microglia cell line (MLS-9) that we developed (1,14,15).…”

mentioning

confidence: 92%

Modulation of the ERG K+ Current by the Tyrosine Phosphatase, SHP-1

Cayabyab¹,

Tsui²,

Schlichter³

2002

Journal of Biological Chemistry

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We reported previously (Cayabyab, F. S., and Schlichter, L. C. (2002) J. Biol. Chem. 277, 13673-13681) a functional interaction between the ERG-1 K ؉ channel and Src tyrosine kinase, which increased the current. We now show that the tyrosine phosphatase, SHP-1, which is present in microglia, is increased after brain damage, and is activated by colony-stimulating factor-1, associates with ERG-1 and regulates the current. Patch clamp recordings from the MLS-9 microglia cells were made with pipette solutions containing a recombinant SHP-1 protein: wild type (SHP-1 wild type (wt)), catalytically active (SHP-1 S6), or the substrate-trapping mutant (SHP-1 Cys 3 Ser). SHP-1 wt and SHP-1 S6 proteins decreased the current, an effect that was reversed by the phosphatase inhibitor, pervanadate, whereas SHP-1 Cys 3 Ser increased the current. Moreover, transient transfection with cDNA for SHP-1 wt or SHP-1 S6 decreased the ERG current without decreasing the protein level. Tyrosine phosphorylation of ERG-1 was decreased by transfection with SHP-1 wt and increased by SHP-1 Cys 3 Ser. The decrease in current by active SHP-1 was partly attributed to changes in the voltage dependence of activation and steady-state conductance, whereas inactivation kinetics and voltage dependence were not affected. Our results show that ERG-1 is a SHP-1 substrate constituting the first report that an ion current is regulated by SHP-1. In excitable cells, Kϩ channels set the membrane potential (V m ), which is crucial for regulating excitability, Ca 2ϩ influx, and secretion. Their roles in non-excitable cells may be even more diverse. In addition to controlling V m and Ca 2ϩ entry, K ϩ channels contribute to ion homeostasis, cell cycle, proliferation, differentiation, apoptosis, and to cell volume regulation, which counteracts metabolically generated osmolytes. The human ether-à -go-go-related gene (HERG) 1 was originally thought to be heart-specific, where its natural mutations underlie one type of life-threatening arrhythmia (2-4). However, HERG and ether-à -go-go K ϩ channels are expressed in certain cancers, leading to intense interest in their contributions to proliferation and cell survival (5, 6). We recently provided the first direct evidence of a functional role for HERG in cancer cells (7). HERG was selectively up-regulated in primary leukemias and several hematopoietic cell lines, and the HERG-channel blocker, E-4031, reduced proliferation in some of the cell lines. HERG and the three known rat ERG isoforms are expressed in the nervous system, and although ERG-2 was thought to be restricted to a small subpopulation of neurons (8), we found ERG-2 mRNA in rat microglia (1). ERG channels in neurons can modulate the resting potential (9), spike frequency (10), hormonal secretion (11, 12), and neuritogenesis (9, 13), although some roles have only been studied in cell lines. We previously identified ERG currents and ERG-1 protein in the brain microglia cell line (MLS-9) that we developed (1, 14, 15). Because MLS-9 cells lack the Kv1.3 and clas...

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“…In addition to carotid body type I cells (41), there is evidence that HERG-like K ϩ channels influence resting membrane potential and excitability in other neuronal cells types such as rat microglia, lactotrophs, chromaffin cells, and mammalian neuroblastoma cells (2,3,6,17,26,48,57). In some cell types, where HERG-like currents govern resting membrane potential, HERG channel blockers have been reported to cause substantial cell membrane depolarization from resting E m (e.g., Ref.…”

Section: Presence Of Herg-like Kmentioning

confidence: 99%

“…Although the best known example of a HERGmediated K ϩ current is the rapidly activating delayed rectifier K ϩ current (I Kr ) in cardiac myocytes (47; reviewed in Ref. 49), HERG-like K ϩ channels are also involved in resting membrane potential regulation, secretion, and suppression of excitability in cell types of neural crest origin, including neuroblastoma cell lines, neuroendocrine tumor cells, and lactotrophs (2,6,7).…”

mentioning

confidence: 99%

Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells

Kim¹,

Boyle²,

Carroll³

2005

Journal of Applied Physiology

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ϩ currents that inhibit hypoxia-induced depolarization and that a decrease in this current with age could underlie, in part, the developmental increase in type I cell depolarization response to hypoxia. In dissociated type I cells from 0-to 1-and 11-to 16-day-old rats, using perforated patch-clamp and 70 mM K ϩ extracellular solution, we measured repolarization-induced inward K ϩ tail currents in the absence and presence of E-4031, a specific HERG channel blocker. This allowed isolation of the E-4031-sensitive HERG-like current. E-4031-sensitive peak currents in type I cells from 0-to-1-day-old rats were 2.5-fold larger than in cells from 11-to 16-day-old rats. E-4031-sensitive current density in newborn type I cells was twofold greater than in cells from 11-to 16-day-old rats. Under current clamp conditions, E-4031 enhanced hypoxia-induced depolarization in type I cells from 0-to-1-day-old but not 11-to 16-day-old rats. With use of fura 2 to measure intracellular Ca 2ϩ , E-4031 increased the cytosolic Ca 2ϩ concentration response to anoxia in cells from 0-to-1-day-old but not cells from 11-to 16-day-old rats. E-4031-sensitive K ϩ currents are present in newborn carotid body type I cells and decline with age. These findings are consistent with a role for E-4031-sensitive K ϩ current, and possibly HERG-like K ϩ currents, in the type I cell hypoxia response maturation.human ether-a-go-go-related gene; potassium channel; hypoxia THE CAROTID BODY chemoreceptors mediate ventilatory and other defensive responses to hypoxic stress in mammals (11,23,28) and appear to be important for survival during postnatal maturation (14,21,28). Despite their importance, the carotid chemoreceptors in neonates exhibit low sensitivity to hypoxia compared with adults and become more sensitive over the first few weeks of life. This process, termed "resetting" of carotid body O 2 sensitivity, occurs in all mammalian species studied to date (8,9,12,20,29,36,37

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A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs

Cited by 66 publications

References 34 publications

Functions of erg K⁺ channels in excitable cells

Functions of erg K⁺ channels in excitable cells

Modulation of the ERG K+ Current by the Tyrosine Phosphatase, SHP-1

Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells

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A functional role of the erg-like inward-rectifying K+ current in prolactin secretion from rat lactotrophs

Cited by 66 publications

References 34 publications

Functions of erg K+ channels in excitable cells

Functions of erg K+ channels in excitable cells

Modulation of the ERG K+ Current by the Tyrosine Phosphatase, SHP-1

Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells

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Functions of erg K⁺ channels in excitable cells

Functions of erg K⁺ channels in excitable cells